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The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression

2021Artigo científico Acesso aberto
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dc.contributor.authorSantos, Sónia Sá
dc.contributor.authorMoreira, João B.
dc.contributor.authorCosta, Márcia
dc.contributor.authorRodrigues, Rui S.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorXapelli, Sara
dc.contributor.authorSolá, Susana
dc.date.accessioned2023-09-28T16:04:31Z
dc.date.available2023-09-28T16:04:31Z
dc.date.issued2021
dc.descriptionCopyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).pt_PT
dc.description.abstractNeural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience.pt_PT
dc.description.sponsorshipThis work was supported by grants PTDC/MED-NEU/29650/2017, UIDB/04138/2020 and UIDP/04138/2020 from Fundação para a Ciência e a Tecnologia, Lisboa, Portugal.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCells. 2021 Dec 29;11(1):90pt_PT
dc.identifier.doi10.3390/cells11010090pt_PT
dc.identifier.eissn2073-4409
dc.identifier.urihttp://hdl.handle.net/10451/59502
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationMetabolic Control of Neural Repair by Diet and Gut Microbiome during Aging
dc.relationResearch Institute for Medicines
dc.relationResearch Institute for Medicines
dc.relation.publisherversionhttps://www.mdpi.com/journal/cellspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectSIRT3pt_PT
dc.subjectAgingpt_PT
dc.subjectDepressionpt_PT
dc.subjectLipid metabolismpt_PT
dc.subjectMitochondriapt_PT
dc.subjectNeural stem cellspt_PT
dc.titleThe mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depressionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/MED-NEU/29650/2017
oaire.awardNumberUIDB/04138/2020
oaire.awardNumberUIDP/04138/2020
oaire.awardTitleMetabolic Control of Neural Repair by Diet and Gut Microbiome during Aging
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleResearch Institute for Medicines
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-NEU%2F29650%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
oaire.citation.titleCellspt_PT
oaire.citation.volume11pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameMoreira
person.familyNameRodrigues
person.familyNameSebastião
person.familyNameXapelli
person.familyNameZeferino Solá da Cruz
person.givenNameJoão
person.givenNameRui S
person.givenNameAna M
person.givenNameSara
person.givenNameSusana
person.identifier129383
person.identifierM-5251-2013
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-id7110-C8C3-ED42
person.identifier.ciencia-id6E11-707D-B0DC
person.identifier.orcid0000-0002-7736-844X
person.identifier.orcid0000-0002-9343-745X
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0001-6854-2509
person.identifier.orcid0000-0003-2036-797X
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id8721560200
person.identifier.scopus-author-id7004195841
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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